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The New York State Office of Addiction Supports and Services (NYS OASAS) has released guidance on xylazine, an animal tranquilizer that has made its way into the US Drug Supply.


 NYS OASAS Medical Advisory Panel (MAP) Xylazine Guidance 

Xylazine, a non-opioid sedative commonly used in veterinary medicine, has become increasingly prevalent in the unregulated drug supply in the United States. While the presence of xylazine is underreported likely both in its geographic distribution and in its contribution to overdose deaths, available data indicate xylazine is widespread and impacting overdose mortality throughout the country. 

Although found in combination with other substances, xylazine is found in the unregulated drug supply most commonly with illicitly manufactured fentanyl, which will be called “fentanyl” for the purposes of this document. Ethnographic research suggests there is an ecological connection with xylazine being added intentionally to fentanyl to potentiate the opioid’s effects. Unlike fentanyl, xylazine is diverted from veterinary sources and introduced into the unregulated drug supply, but it is unknown at what point it is introduced. Because xylazine is approved by the U.S Food and Drug Administration (FDA) for use in veterinary medicine only, it is not classified as a controlled substance under the U.S. Controlled Substances Act. 

As the prevalence of xylazine has increased in the unregulated drug supply, there have been subsequent increases in the number of hospitalizations for skin wounds associated with substance use. Xylazine can cause skin wounds that are not associated with environmental factors (such as living unhoused and/or lacking access to hygiene facilities), but rather with use of the substance itself. These complex wounds often occur at skin sites associated with injection, but they can occur at skin sites that are not associated with injection and in individuals who don’t inject substances. Early intervention in treating xylazine-related skin wounds can prevent them from progressing into severe necrotic skin ulcerations.

Because of xylazine’s increasing presence in the unregulated drug supply, people who use drugs (PWUD) are interested in having the ability to test their substances for xylazine prior to using them. Immunoassay drug checking technology, like fentanyl test strips, provide the framework and possible implementation pathway for similar xylazine testing technology within communities. Xylazine test strips have been researched, and initial findings indicate their validity and utility; they are now available commercially. 

Surveillance and point-of-care drug checking programs also are becoming more widely available to help both communities and PWUD test local drug supplies. In New York State, the currently available data indicate xylazine is present in the unregulated drug supply and contributing to overdose deaths throughout the state. Research conducted by the New York City Department of Health and Mental Hygiene (NYC DOHMH) using gas chromatography/mass spectrometry (GC-MS) drug checking technology found that 2.2% of the 357 sampled syringes collected by NYC DOHMH through syringe services program partners were positive for xylazine in 2017. More recent drug checking programs piloted by the NYC DOHMH using Fourier Transform Infrared (FTIR) technology have found xylazine present exclusively in fentanyl samples. In 2021, xylazine was involved in 19% of the opioid-involved overdose deaths in NYC.

 Early History, Ethnographic Research, and Epidemiology of Xylazine 

Ethnographic research, exploring cultural phenomena through qualitative interviews and real-life observation, combined with drug checking research have provided valuable insight into the experiences of people using substances with xylazine present. Early research on xylazine in the unregulated drug supply began in Puerto Rico in 2005 after local harm reduction programs observed deep sedation and severe skin wounds within communities of PWUD. At that time, confirmatory testing using GC-MS indicated xylazine was present in 37.6% of the used syringes collected across 11 municipalities in Puerto Rico. Xylazine was found commonly with both opioids and cocaine and was prevalent especially in cattle-farming towns. However, 22% of the participants whose syringes tested positive for xylazine reported that they did not use xylazine, indicating it may have been an unknown additive in the unregulated drug supply at the time. 

By 2007, xylazine use in Puerto Rico during the previous 30 days had reached over 80% of the sampled population.16 Ethnographic research from that time found that PWUD were aware of xylazine’s presence in the unregulated drug supply and had used the substance both knowingly and unknowingly. This early research pointed to recognizable signs of xylazine based on the substance’s sedative effect, taste, dark brown color, and strong odor. Skin wounds were the primary identified health concern, but the research also described the need for clinical recognition and support for xylazine withdrawal and chronic xylazine use.

In 2006, xylazine began appearing in medical examiner’s reports in Philadelphia, making it the first city in the contiguous United States to report xylazine use. Although it wasn’t highly prevalent in the medical examiner’s reports initially, as xylazine’s presence as an additive in the unregulated drug supply began to increase, there were subsequent increases in xylazine-involved overdose deaths. By 2021, xylazine had become the most common adulterant in Philadelphia’s unregulated drug supply with 91% of samples sold as “dope” containing xylazine. Ethnographic research indicated that by that time, PWUD in Philadelphia largely were aware of xylazine’s presence in the unregulated drug supply and had mixed preferences for using the substance or avoiding it.

Since then, xylazine has spread within the Northeast and continued westward and southward. U.S Drug Enforcement Administration (DEA) forensic laboratory testing showed significant increases in the presence of xylazine across all geographic regions in the United States between 2020 and 2021. While the Northeast had the highest total of xylazine-positive samples, the largest percentage increases were found in the South (193% increase) and the West (112% increase). The most recent available data from April 2021 through March 2022 found xylazine-positive samples in 25 of the 39 states where xylazine toxicology testing was ordered in primary care settings, indicating that xylazine has been incorporated widely into the unregulated drug supply throughout the United States.

Xylazine-Involved Overdose Deaths 

Xylazine’s presence in the unregulated drug supply, and its contribution to overdose deaths, is widespread and increasing. Xylazine is an alpha-2 adrenergic agonist that causes profound sedation and central nervous system (CNS) depression. This can contribute to a blunted response to airway occlusion much like the effects from other sedatives such as benzodiazepines and barbiturates. Because of xylazine’s co-occurrence with fentanyl, the sedation that it causes has synergistic effects with the respiratory depression caused by opioids, contributing to increases in overdose mortality. 

Xylazine likely is highly underrecognized in most overdose situations and because this substance is not an opioid, xylazine overdose is not responsive to naloxone. Naloxone has become the standard, and often the only, response to overdoses. However, most overdoses involve multiple substances, making polysubstance overdose recognition and response an important strategy to reduce overdose deaths. Xylazine often is mixed in with fentanyl, therefore naloxone administration still is the first recommended step in responding to an overdose; however, it should be followed by other lifesaving interventions such as rescue breathing.